Creutzfeldt-Jakob disease (CJD) is a rare fatal neurodegenerative disorder caused by abnormal prion agents. Transmissibility of the classic forms of CJD by blood transfusion is currently unknown. The proposed project will continue the only active, nationwide look-back study on recipients of blood products from donors subsequently diagnosed with classic CJD. This study began in 1995, and has been working for the past 20 years on the key objective of carefully and systematically assessing the risk of blood borne transmission of this disease in the United States. The major components of the study include collaboration with multiple sources to identify blood donors diagnosed with classic CJD in the United States; working with blood centers to trace the blood components from donors diagnosed with classic CJD to final disposition; collecting vital status and cause of death information (if applicable) on the recipients of blood components; utilizing the data from the study to continually monitor and assess the risk of blood-borne transmission of CJD; and disseminating results of the study to relevant stakeholders. To date, the study has enrolled 54 blood donors who died of classic CJD and 666 recipients of their blood. Through 2013, 125 of these recipients were presumed to be still alive, 520 were deceased and 21 were lost to follow-up. Post transfusion, these three groups had survived a total of 2719.5 person-years. A total of 187 recipients survived five years or longer post transfusion and 86 of them had received blood donated 60 or fewer months before the onset of CJD in the donor. No recipients with CJD have been identified. The current results of this large, ongoing look-back study show no evidence of transfusion transmission of CJD. They reinforce the conclusion that the risk, if any, of transfusion transmission of prion disease by classic CJD donors is significantly lower than the comparable risk of such transmission by vCJD donors.